Retinitis pigmentosa (RP) is a broad description for pigment changes and/or damage in the retina. A hereditary form of retinitis pigmentosa called autosomal dominant retinitis pigmentosa (AdRP) is a degenerative disease that typically causes blindness by middle age. Bird A C, American journal of ophthalmology 1995; 119:543-562; Boughman J A et al. Am J Hum Genet 1980; 32:223-235; Schuster A et al. Br J Ophthalmol 2005; 89:1258-1264. AdRP is caused by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina leading to progressive sight loss. AdRP patients may experience defective light to dark, dark to light adaptation or night blindness as the result of the degeneration of the peripheral visual field. AdRP results in loss of photoreceptor (rods) cells from peripheral retina and then cones from central retina.
Over 100 rhodopsin mutations have been identified in patients with AdRP. Sullivan L S et al. Invest Ophthalmol Vis Sci 2006; 47:3052-3064; Wang D Y et al. Clinica chimica acta; international journal of clinical chemistry 2005; 351:5-16. The P23H mutation is the most prevalent mutation and is present in ˜25% of AdRP and 5-15% of RP cases. Dryja T P et al. Proc Natl Acad Sci USA 1991; 88:9370-9374. Mutant rhodopsin protein such as P23H has a toxic gain-of-function that induces misfolding and disruption of normal rhodopsin protein, which leads to photoreceptor cell apoptosis. Typically, rods degenerate first, affecting low light vision. Then, cones degenerate, affecting bright light and color vision. The age of onset is variable with gradual progressive reduction in night and peripheral vision, often leading to “gun-barrel” visual field or tunnel vision. Median age of night-blindness onset is 12-14 years old. Blindness is frequent in middle ages and most rod cells are lost by age 40.